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Supplemental Digital Content is available in the text, Objective: To investigate whether [18F]fluorothymidine (FLT) and/or [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate growth in neurofibromatosis 2 (NF2) related vestibular schwannomas (VS) and to evaluate the importance of PET scanner spatial resolution on measured tumor uptake. Methods: Six NF2 patients with 11 VS (4 rapidly growing, 7 indolent), were scanned with FLT and FDG using a high-resolution research tomograph (HRRT, Siemens) and a Siemens Biograph TrueV PET-CT, with and without resolution modeling image reconstruction. Mean, maximum, and peak standardised uptake values (SUV) for each tumor were derived and the intertumor correlation between FDG and FLT uptake was compared. The ability of FDG and FLT SUV values to discriminate between rapidly growing and slow growing (indolent) tumors was assessed using receiver operator characteristic (ROC) analysis. Results: Tumor uptake was seen with both tracers, using both scanners, with and without resolution modeling. FDG and FLT uptake was correlated (R2 = 0.67–0.86, p

[Profound alterations in metabolism occur within the first few minutes of myocardial ischaemia which may induce or modulate myocardial electrophysiological abnormalities and arrhythmogenesis, Fatty acid oxidation is inhibited with accumulation of long-chain acyl CoA esters and glycolysis is stimulated but later inhibited. This may be worsened by a peripheral sympathetic response. In particular regional variations in glycolytic ATP productions which can modulate "slow channel" ion flux and hence slow conducting "slow response" potential activity, could influence patterns of slow conduction in ischaemic myocardium of importance in generating early re-entrant arrhythmias. This possibility has been examined in open chest anaesthetised dogs following experimental coronary occlusion by detailed computer aided analysis and construction of three dimensional maps of regional metabolism, blood flow and epicardial activation patterns at the time of early ventricular arrhythmias. Activation patterns were obtained using an electronic multiplexing system, flow using tracer microspheres and metabolic changes by analysis of multiple tissue samples for lactate and indices of glycolytic activity after rapid excision and freezing of the heart. Marked spacial inhomogeneities in flow, lactate and glycolytic activity were associated with delayed and fragmented activation in the central ischaemic region. Within the border region of flow, however, glycolytic activity was enhanced and conduction generally little impaired. It is suggested that transient changes in the homogeneity of myocardial metabolism and flow are critical in determining patterns of conduction and hence arrhythmogenesis. This may provide a basis for understanding anti-arrhythmic effects of metabolic interventions.

The discipline of perioperative medicine is assuming greater importance as increasing numbers of older patients with medical comorbidity undergo complex surgical procedures. If patient outcomes and use of limited hospital resources are to be optimized, physicians with skills and interest in perioperative risk assessment and therapeutic intervention are needed. This systematic review attempts to provide an evidence-based update in several key areas in the management of the perioperative patient.

The advent of insulin treatment in 1923 meant fewer diabetes deaths from acute metabolic deterioration and sepsis and a progressive increase in the burden of disease caused by end-organ damage. These diabetic complications are the major cause of morbidity and premature mortality among diabetic subjects. Over the last 50 years it has become apparent that diabetic complications in disparate tissues may result from a combination of common pathological processes. Pathways activated by initial metabolic insults are promoted by co-factors such as renin-angiotensin-aldosterone system activation, hyperinsulinaemia, underlying genetic susceptibility, and traditional vascular risk factors, particularly hypertension and lipids. These common pathways include AGE formation, reactive oxygen species overproduction, protein kinase C activation, mitochondrial dysfunction and activation of proinflammatory and profibrotic signalling cascades. Once established, these interlinked pathways become self-perpetuating. Many drugs acting against individual downstream targets in these pathways have failed due to lack of efficacy or adverse effects. Gains in the future may be made by better control of existing risk factors, more sophisticated modulation of tissue glucose and insulin signalling, and interventions to improve mitochondrial function and reduce oxidative stress. Epigenetic and microRNA research may lead to methods to disrupt the mechanisms whereby pathological pathways are perpetuated. Expansion in capacity and expertise in biomarker measurement and analysis may allow better targeting of therapies to patients who are most likely to benefit. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).

OBJECTIVE—To determine whether changes in plasma concentrations of β endorphins alter angina threshold and peripheral pain threshold in patients with stable angina. DESIGN—Latin square design comparison of angina thresholds by exercise treadmill test and peripheral pain thresholds using a radiant heat source in eight patients with stable angina under control conditions, after stimulation of pituitary β endorphin release by ketoconazole, after suppression of pituitary β endorphin release by dexamethasone, and after blockade of opioid receptors by intravenous naloxone. RESULTS—An approximately fivefold increase in circulating concentrations of β endorphins was found after administration of ketoconazole (mean (SEM): 13.9 (1.2) v 73.8 (6.2) pg/ml; p

Purpose: Gradual drifting of baseline signal intensity is common in functional MRI (fMRI) time course data. Methods for dealing with this effect are studied. Method: Simulations and fMRI data are used to study three statistical models that account for baseline drift. A method is proposed in which the time course data are linear least-squares fit to a reference function that includes the slope of the baseline drift as a free parameter. Results: It is shown that the least-squares method is equivalent to cross-correlation with Gram-Schmidt orthogonalization. Additionally, it is shown that certain paradigm designs improve the sensitivity of statistical tests when using any of the drift correction methods commonly employed. The least-squares method results in a variety of useful parameters such as activation amplitude, with a well characterized error. Conclusion: Very simple techniques can effectively account for observed drifts. It is important to design paradigms that are symmetric about the midpoint of the time series. In calculating confidence levels, a proper statistical model that accounts for baseline drifts is necessary to ensure accurate confidence level assessment. Index Terms: Magnetic resonance imaging, functional-Time series analysis.

Brain imaging data are generally used to determine which brain regions are most active in an experimental paradigm or in a group of subjects. Theoretical considerations suggest that it would also be of interest to know which set of brain regions are most interactive in a given task or group of subjects. A subset of regions that are much more strongly interactive among themselves than with the rest of the brain is called here a functional cluster. Functional clustering can be assessed by calculating for each subset of brain regions a measure, the cluster index, obtained by dividing the statistical dependence within the subset by that between the subset and rest of the brain. A cluster index value near 1 indicates a homogeneous system, while a high cluster index indicates that a subset of brain regions forms a distinct functional cluster. Within a functional cluster, individual brain regions are ranked at the center or at the periphery according to their statistical dependence with the rest of that cluster. The applicability of this approach has been tested on PET data obtained from normal and schizophrenic subjects performing a set of cognitive tasks. Analysis of the data reveals evidence of functional clustering. A comparative evaluation of which regions are more peripheral or more central suggests distinct differences between the two groups of subjects. We consider the applicability of this analysis to data obtained with imaging modalities offering higher temporal resolution than PET.

Recombinant human ciliary neurotrophic factor (rh-CNTF) was reported to attenuate skeletal muscle wasting in rats after unilateral transection of the sciatic nerve (M. E. Helgren, S. P. Squinto, H. L. Davis, D. J. Parry, T. G. Bolton, C. S. Heck, Y. Zhu, G. D. Yancopoulos, R. M. Lindsay, and P. S. DiStefano. Cell 76: 493-504, 1994). Under the experimental conditions reported herein, the absolute masses of the denervated gastrocnemius and soleus muscles were not increased in mature or immature rats of either sex by treatment with rhCNTF. At the highest doses of rhCNTF (1 and 0.1 mg/kg), increases in the ratio of the masses of the denervated to the contralateral innervated gastrocnemius and soleus muscles could be attributed entirely to a muscle-wasting effect on the contralateral innervated muscle rather than any muscle-sparing effect on the denervated muscle. The muscle-wasting effects of rhCNTF were associated with reductions in body weight gain and reduced food intake. Pair-fed rats lost less body weight and skeletal muscle mass than rhCNTF-injected freely fed rats but experienced significantly greater loss of visceral mass. Male rats displayed greater loss of body weight and skeletal muscle mass than female rats. Recombinant inhibitors of the cachectic cytokines, tumor necrosis factor and interleukin-1, did not significantly alter the wasting effects of rhCNTF. These findings demonstrate that, in contrast to its well-characterized trophic effects on cells of the nervous system, rhCNTF causes atrophy of skeletal muscle by mechanisms involving both anorexia and cachexia based on the results of pair-feeding experiments.

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

To determine the magnitude and distribution of pressures in breast models subjected to mammographic compression forces.A vinyl-wrapped, unleavened-bread-dough breast model was compressed. Pressures in the dough models were measured with a strain gauge connected to a water-filled sensor.Under broad compression, pressures were uniform (range, 2.76-22.06 kPa [0.4-3.2 psi]). Spot compression increased pressures by as much as 60%. Pressures dropped sharply outside of paddle margins. No pressure differentials were found near small, deep simulated masses. The pressure of large masses increased by 50% when subjected to full compression force. Vigorous digital palpation resulted in a pressure of more than 41.40 kPa (6 psi).General pressures were mild and uniform. Internal pressures varied inversely with the area to which force was applied. Pressure dissemination was restricted by the cohesive binder and allowed zones of greater pressure to form directly under the applied force. The surrounding matrix disseminated pressure and protected small masses; large masses, bearing the force of the paddle, were exposed to greater pressure. Digital palpation administered high pressures.

To assess whether the introduction of a management of raised glucose clinical decision tool could improve assessment of patients with hyperglycaemia by non-specialist physicians, leading to early discharge and improved quality of inpatient care.Participants were adults aged 18 years or over presenting to the Medical Assessment Unit with a capillary blood glucose level11.1 mmol/l. Phase 1 of the study (phase 1) evaluated current clinical practice and potential impact of the clinical decision tool. Phase 2 evaluated the effectiveness of the management of raised glucose tool in clinical practice. Primary outcome measures were inpatient length of stay and same-calendar-day discharges. Secondary outcome measures were diabetes specialist input, patient assessment, intravenous insulin infusion use and patient satisfaction.Implementation of the management of raised glucose clinical decision tool allowed safe, same-calendar-day discharges of 40% of patients with hyperglycaemia as their primary reason for attendance. Median length of stay was lower in the phase 1 than in phase 2 (1.0 vs. 3.5 days, P0.01). Early discharge did not result in an increase in readmissions. There was improvement in hyperglycaemia assessment for all patients (P0.01), a reduction in the use of intravenous insulin infusions (P0.01) and high level of patient satisfaction.The management of raised glucose clinical decision tool resulted in a significant increase in the number of same-calendar-day discharges and reduction in hospital length of stay without adverse impact on readmission rates. Additionally, the tool was associated with improvements in inpatient diabetes care and patient satisfaction.

Children with disabilities and their families experience environmental barriers in the school and community environments. There is a need to understand and appropriately measure environmental factors that influence activity and participation for disabled children. The purpose of this paper is to describe the adaptation process of the Craig Hospital Inventory of Environmental Factors (CHIEF) to make it suitable as a parent proxy measure for disabled children aged 2-12 years.The adaptation process consisted of four steps using data from previous research conducted at CanChild: (i) analysis of item-total correlations from all items on the CHIEF; (ii) frequency of endorsement; (iii) determination of the representativeness of the questions; and (iv) correlations on selected items. Once the items were selected, a test-retest reliability study was conducted.The internal consistencies (α) for the time 1 and time 2 administrations were 0.76 and 0.78, respectively. Test-retest reliability of the questionnaire was ICC = 0.73 for the total product score.The 10-item CHIEF for Children-Parent Version is an acceptable, easy-to-complete and reliable measure of perceived environmental barriers for disabled children 2-12 years of age.

Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We therefore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipoproteins and cholesterol precursors in adult growth hormone deficient patients.Double-blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month).Eighteen patients with severe growth hormone deficiency.Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months.In the rhGH treated group there was a significant fall in serum cholesterol (P0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol (P0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolipoprotein B (P0.01 (1.30 +/- 0.11 to 1.15 +/- 0.11 g/l) and mevalonic acid (P0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 micrograms/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fall in cholesterol (P0.05), LDL cholesterol (P0.01) and apolipoprotein B (P0.01). There were no significant changes in any of the measured variables in the placebo group.We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up-regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.

Adjuvant intravesical Mycobacterium bovis BCG is the treatment of choice for recurrent superficial bladder cancer. Fibronectin (FN) was previously demonstrated to be necessary for the retention of BCG within the bladder and for the expression of antitumor activity. Recent studies have demonstrated that BCG attach and are ingested by bladder epithelial cells, suggesting the existence of a second bacterial attachment mechanism. We report the characterization of the molecules involved in BCG attachment and internalization by the human bladder transitional cell carcinoma cell line T-24. Pretreatment of T-24 cells with monoclonal antibodies to either alpha 5 or beta 1 integrin subunits significantly inhibited both BCG attachment and ingestion. Exogenous FN was observed to enhance both attachment and ingestion of BCG, and anti-FN was observed to inhibit both phenomena. Latex beads precoated with either FN or laminin (LN) but not BSA were ingested by T-24 cells, but only FN-coated beads inhibited BCG attachment and ingestion. Pretreatment of BCG with FN augmented both attachment and ingestion. The role of bacterial FN binding proteins was evaluated. A monoclonal antibody to a 55-kD FN-binding protein was observed to abrogate attachment and ingestion. These results demonstrate that attachment and ingestion of BCG are mediated in part by the alpha 5 beta 1 integrin receptor and are dependent on FN. These studies demonstrate a mechanism of entrance of mycobacteria into epithelial cells and suggest a second role for FN in the adjuvant antitumor effect of BCG.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) infections cause significant morbidity and mortality among liver transplant candidates and recipients. To assess rates of MRSA and VRE colonization, we obtained active surveillance cultures from 706 liver transplant candidates and recipients within 24 h of admission to an 11-bed liver transplant ICU from October 2000 to December 2005. Patients were followed prospectively to determine the cumulative risk of MRSA or VRE infection or death by colonization status. Outcomes were assessed by Kaplan-Meier survival analysis and Cox regression and multivariate logistic regression adjusting for covariates. The prevalence of newly detected MRSA nasal and VRE rectal colonization was 6.7% and 14.6%, respectively. Liver transplant candidates and recipients with MRSA colonization had an increased risk of MRSA infection (adjusted OR = 15.64, 95% CI 6.63-36.89) but not of death (adjusted OR = 1.00, 95% CI 0.43-2.30), whereas those with VRE colonization had an increased risk both of VRE infection (adjusted OR = 3.61, 95% CI 2.01-6.47) and of death (adjusted OR = 2.12, 95% CI 1.27-3.54) compared with noncolonized patients. Prevention and control strategies, including use of active surveillance cultures, should be implemented to reduce the rates of both MRSA and VRE colonization in this high-risk patient population.

Carbamazepine (CBZ) is a widely used antiepileptic drug (AED). Recently, a chewable tablet (Tegretol chewtabs) has been formulated. This open substitution study was designed to compare the two formulations with respect to efficacy and tolerability in patients with intractable epilepsy. Thirty patients (24 males, 6 females, mean age 46 years, range 28-83) were studied. Duration of epilepsy was 21-68 years (median 34 years). Four patients were taking CBZ monotherapy, 17, 6 and 3 patients were respectively taking CBZ plus 1, 2 and 3 additional AEDs. Upon entry to study, patients were switched to an equivalent dose of chewtabs and subsequently evaluated at 2, 4, 8 and 12 weeks. Two patients did not complete the study. On entry, the mean 14 day seizure rate was 2.5. On chewtabs mean 14 day rates were 2.4, 2.2, 2.4 and 2.7 after 2, 4, 8 and 12 weeks of treatment respectively. On entry the mean steady state trough serum CBZ concentration was 35 mumols/l compared to 32, 31, 32 and 34 mumols/l after 2, 4, 8 and 12 weeks respectively. Nineteen patients were classified showing good or excellent tolerability, 7 satisfactory and 2 fair. In conclusion, chewtabs were essentially equivalent to the conventional formulation in efficacy and tolerability. After 12 weeks treatment, 19 patients preferred the chewable formulation.

The treatment of diabetes was revolutionised shortly after the turn of the twentieth century by the extraction and purification of insulin. Methods to protract (i.e. prolong) the action of insulin were developed in the 1930s; little changed in the technology of insulin protraction until the turn of this century when, with renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, technology advanced again. Two new long-acting insulin analogues have come to the market; some may be familiar with insulin glargine, which has been widely used for some years now. This review attempts to describe the novel method of protraction that insulin detemir (launched last summer) employs by albumin binding, to discuss the possible therapeutic benefits of this method of protraction and to describe the findings of studies comparing insulin detemir with other currently available long-acting insulin preparations. The intention of this article is not to review all of the currently available long-acting insulin analogues.

In an azotemic patient with suspected renal artery stenosis, undiluted gadopentetate dimeglumine was administered in an aortic bolus to provide contrast at digital subtraction angiography of the aorta and renal arteries. The contrast material (5 mmol/mL) was power injected (rate, 15 mL/sec; total dose, 30 mL). Selective renal arteriography was also performed with 5 mL of undiluted gadopentetate dimeglumine hand injected into each renal artery (total dose, 40 mL). The patient tolerated the procedure without complication or worsening of renal function, and diagnostic angiographic images were obtained.

The past five years has seen much activity in the United Kingdom into the preparation for dealing with chemical incidents For accident and emergency (A&E) departments, many chemical incidents occur each year. However, surveillance suggests that few incidents occur in any one department each year as probably not more than about 10 events are reported for each A&E.1 The problem of A&E departments failing to manage incidents effectively has been reported.23 With little routine experience from any hazardous material incident or chemical incident, building the necessary skills to achieve the maximisation of patient care and the minimisation of harm to staff and hospital facilities has been difficult. Therefore, the need to prevent problems arising from a chemical incident, be it accidental or deliberate, for an A&E department has …

This case report describes the initial presentation of variant CJD to a general dental practitioner. The case highlights the importance of prompt referral of patients presenting with a history of atypical facial symptoms.

Growth hormone (GH) is known to be required for physical well-being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD).A double-blind, placebo-controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH-deficient adults, where nine continued with GH replacement.GH-treated adults (10 men, 11 women), all with severe GHD (peak GH7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years).Semi-structured interviews were given at baseline and end-point plus questionnaires that included a new hormone-deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well-being Index (GWBI), the Well-being Questionnaire (W-BQ12), the Short-Form 36 health status questionnaire (SF-36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ).Three months after baseline the serum total IGF-I of placebo-treated patients fell from normal, age-related levels (mean 26.6 +/- 13.2 nmol/l) to levels indicative of severe GHD (11.6 +/- 6.6 nmol/l) (P0.001). Psychological symptoms of GH withdrawal, reported in interviews at end-point by placebo-treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end-point (chi2=11.25, P0.01). Significant between-treatment-group differences in change scores were found for SF-36 General Health (P0.01), W-BQ12 Energy (P0.01) and HDQoL do physically (P0.05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo-treated group at end-point relative to GH-treated patients.Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.

To evaluate the psychometric properties of two health status measures for adults with growth hormone deficiency (GHD): Nottingham Health Profile (NHP) and Short-Form Health Survey (SF-36).(1) A cross-sectional survey of adults with treated or untreated GHD to assess reliability and validity of the questionnaires. (2) A randomized, placebo-controlled study of 3 months' GH withdrawal from GH-treated adults to assess the sensitivity of the questionnaires to change.(1) A cross-sectional survey of 157 patients with severe GHD (peak GH10 mU/l on provocative testing), mean age 48.9 years (range 23-70 years), who had either received GH replacement therapy for at least 6 months immediately prior to the study or had not received GH treatment in the previous 6 months. (2) GH treatment was withdrawn from 12 of 21 GH-treated adults, all with severe GHD (peak GH7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years).The NHP and SF-36 were used once in the cross-sectional survey, but twice in the GH-withdrawal study, at baseline and end-point (after 3 months).(1) Cross-sectional survey. Both questionnaires had high internal consistency reliability with subscale Cronbach's alphas of0.73 (NHP) and0.78 (SF-36). Calculation of an NHP Total Score, occasionally reported in the literature, was shown to be inadvisable. Overall, patients with GHD were found to have significantly worse perceived functioning than the UK general population in SF-36 subscales of General Health, Bodily Pain, Social Functioning, Physical Functioning, Role-Emotional, Role-Physical, and Vitality. Although neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations with duration of GH treatment (P0.01) for GH-treated patients in SF-36 Mental Health (r = 0.29, N = 87) and SF-36 Vitality (r = 0.33, N = 88), indicating improvement with increasing treatment duration. The SF-36 was also more sensitive than the NHP to sex differences: men had significantly better health status compared with women (P0.05) in all SF-36 subscales but Mental Health, but only in one NHP subscale (Physical Mobility). (2) GH-withdrawal study. Significant between-group differences in change were found in SF-36 General Health [t(17) = 2.76, P = 0.013, two-tailed] and SF-36 Mental Health [t(17) = 2.41, P = 0.027, two-tailed]: patients withdrawn from GH reported reduced general health and mental health at end-point. The NHP found no significant change.The SF-36 is a better measure than the NHP of health status of people with GH deficiency because of its greater discriminatory power, with ability to detect lesser degrees of disability. It also has superior sensitivity to some subgroup differences and superior sensitivity to change compared with the NHP. The SF-36 is highly acceptable to respondents, and has very good internal consistency reliability. The SF-36 is recommended to measure the health status of adults with GH deficiency.

Specific problems in patients with insulin-dependent diabetes mellitus (IDDM) and GH deficiency are hypoglycaemic attacks, increased insulin sensitivity and loss of energy. These problems may be related to GH deficiency.GH replacement was initiated in five patients with type 1 diabetes mellitus and GH deficiency for 6 months [four males and one female, mean age 41.6 +/- 3.8 years, mean +/- standard error of the mean (SEM); body mass index (BMI) 22.3 +/- 1.2 kg/m2].Body composition (bioimpedance), metabolic control [haemoglobin A1C (HbA1C)], insulin requirement and frequency of hypoglycaemia were measured, and quality of life was assessed using validated questionnaires. Monthly eye photographs were taken.IGF-I concentrations were below the age-adjusted range at baseline and increased significantly following GH replacement therapy [analysis of variance (ANOVA), P0.05]. Diabetes control as assessed by HbA1C remained stable (8.2 +/- 0.2 vs. 8.0 +/- 0.4), but needed a 1.75-fold increase in insulin dose/day. Lean body mass tended to increase (P = 0.07) and body fat mass decreased significantly (P0.01). Number of severe hypoglycaemic (3 mmol/l) attacks decreased significantly (P0.04) and quality of life assessed by validated questionnaires improved significantly in all patients [Psychological and General Well-Being Schedule (PGWBS), P0.04; Nottingham Health Profile (NHP), P0.05]. Monthly eye photographs revealed no changes in the retina in any patients.GH replacement therapy has a beneficial effect at the dose used. It restores body composition and decreases frequency and severity of hypoglycaemic episodes, thus improving quality of life. Long-term trials are needed to determine the safety of GH replacement therapy in these patients.

Patients with type 1 diabetes are at increased risk of cardiovascular disease, which may be related to abnormal lipid metabolism. Secretion and clearance of VLDL apolipoprotein B100 (apoB) are important determinants of plasma lipid concentrations and are known to be influenced by hormones, including insulin and growth hormone.This study examined overnight VLDL apoB metabolism and VLDL composition in six lean patients with type 1 diabetes during euglycaemia (controlled by a varying insulin infusion) and in six age-, sex- and BMI-matched control subjects.VLDL apoB kinetics were determined using a primed constant 1-13C leucine infusion, and VLDL apoB enrichment was measured by gas-chromatography mass-spectrometry. Fasting lipid profile, IGF-I, IGFBP-3, overnight GH profiles and free insulin concentrations were also assessed.Fasting concentrations of triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) were similar in both groups. The VLDL apoB secretion and metabolic clearance rates were not significantly different between the two groups, but the VLDL-TGNLDL apoB and the VLDL-CNLDL apoB ratios were significantly increased in those with diabetes (P0.02 and P0.03, respectively). Total IGF-I concentrations were similar between the two groups; however, the GH area under the curve and free insulin concentrations were increased in patients with type 1 diabetes (GH: diabetes: 94.8 +/- 15.1 vs. controls: 45.6 +/- 10-6, mU/L/h, P0.04; free insulin: diabetes: 78.4 +/- 5.0 vs. controls: 28.3 +/- 3.26, pmol/l, P0.001). IGFBP-3 concentrations were lower in diabetic patients (diabetes: 2,454.2 +/- 68.7 vs. controls: 3,219.4 +/- 76.4, ng/ml, P0.001). In the control group overnight GH secretion correlated negatively with fasting TC (P0.01) and LDL-C (P0.03) concentrations, whereas free insulin concentrations correlated positively with fasting TG concentrations (P0.009). No significant correlations were found in the patients with diabetes.This study suggests that in euglycaemic conditions patients with type 1 diabetes mellitus have normal VLDL apoB kinetics but altered VLDL composition. The altered VLDL composition may be associated with accelerated atherogenesis. We speculate that the disrupted hormonal balance and, in particular, the increased GH secretion might be responsible for the compositional changes of VLDL particles in type 1 diabetes mellitus.

To determine the pharmacokinetics and absolute bioavailability of risedronate after single-dose oral administration of 30 mg risedronate as a tablet and an aqueous solution, and 0.3 mg risedronate as an intravenous infusion.This study was a randomized, three-treatment, four-period, partial replicate crossover study involving 33 healthy volunteers. Treatments were administered 7 weeks apart, and the third treatment was repeated during the fourth period. Serum and urine were collected over 72 hours and 672 hours, respectively.Following intravenous administration, renal clearance accounted for 87% of total clearance, with 65% of the dose excreted within 24 hours and 85% of the dose excreted within four weeks. The absolute bioavailability was approximately 0.62% after both oral formulations, and the relative bioavailability of the tablet compared with the oral solution was 104%. The rate and extent of absorption from the two formulations were bioequivalent based on the range proposed for highly variable drugs. Intrasubject variability following oral administration was 50-80%, and was primarily associated with absorption.The majority of the total clearance after intravenous administration of risedronate was renal clearance, indicating that only a small percentage of a systemic dose is potentially incorporated, or "cleared," into bone. The absolute bioavailability of orally administered risedronate is approximately 0.6%, and is independent of formulation. Variability in the pharmacokinetics following oral administration is primarily associated with intrasubject variability in absorption.

To report the prevalence of obesity and body fat distribution in the New Zealand population and to determine if there is a trend to increasing obesity and changes in body fat distribution.Body weight, height, two skinfolds (triceps and subscapular), and waist and hip circumferences were measured on 4,420 New Zealanders as part of the 1997 National Nutrition Survey (NNS97). These results are compared with data from the 1977 National Heart Foundation Survey (n=1,800) and the 1989 Life in New Zealand Survey (LINZ89) (n=3,300).35% of the population (40.4% males, 30.1% females) were classified as overweight and a further 17% as obese (14.7% males, 19.2% females) in NNS97 compared to 32% overweight and 11% obese in LINZ89. Body weight and body mass index have increased in the last two decades. In addition, there has been an increasing trend towards central obesity as estimated by waist to hip ratio and subscapular to triceps ratio.The increase in body weight, obesity, central obesity, and the proportion of the population likely to exhibit health risk indicators presents an increasing health problem in New Zealand.

To examine the adequacy of calcium intake in relation to current recommendations, demographic differences in calcium intake and dietary sources in the New Zealand population.24-hour diet recall and qualitative food frequency data from the 1997 New Zealand National Nutrition Survey (NNS97) were used.No age-gender subgroups had median intakes meeting the latest (1998) US recommendations. Women's median intakes failed to meet even the considerably lower 1990 Australian recommendations. 20% of New Zealanders and one in four women had intakes below the UK Estimated Average Requirements for calcium. Intakes below the UK Lower Reference Nutrient Intake (the level at which the risk of deficiency is virtually 100%) were common (15-20%) among women aged 15-18 years, those living in the most deprived areas or Maori. Milk and milk products were the major sources of the nation's calcium intake.Although other factors such as genetics, hormonal status, vitamin D status and exercise influence skeletal health, adequate calcium intakes are important in minimizing bone loss. A reduction in the proportion of New Zealanders with inadequate calcium intakes will most readily be achieved if more people meet the milk products Dietary Guideline (minimum of two servings daily). Health professionals can play an important role in raising perceptions of the benefits of adequate calcium intakes, promoting the milk products Dietary Guideline, and emphasising that lower fat diets can include adequate calcium through use of reduced fat milk products.

To assess dietary iron intakes and biochemical iron status of a nationally representative sample of nonpregnant 15-49 year old women (n=1,751) in New Zealand.A cross-sectional national survey was conducted in 1996/97. Women were selected via a multistage stratified cluster sampling procedure with increased sampling of Maori and Pacific women. Dietary iron intakes were estimated using a 24-hour diet recall. Biochemical iron status was assessed on a non-fasting venipuncture blood sample (n=1,047) via haemoglobin, mean cell volume, erythrocyte zinc protoporphyrin, transferrin receptors and serum ferritin.Average daily dietary iron intakes ranged from 9.6 mg/day among Pacific women to 10.5 mg/day among Maori women; 41% of 20-49 year olds and 45% of adolescents were at risk of low dietary iron intakes. The estimated percentage of 15-49 year old women with iron deficiency anaemia ranged from 1.4-5.5%, and for iron deficiency without anaemia from 0.7-12.6% depending on the age group and criteria used.The overall estimated prevalence of suboptimal biochemical iron status among 15-49 year old women in New Zealand ranged from 7-13%, which compared favourably with premenopausal women living in other western countries. This situation is, however, a public health concern given the potential negative functional consequences associated with even mild iron deficiency.

To describe the development and use of the methodologies in the 1997 New Zealand National Nutrition Survey (NNS97).NNS97 was a voluntary cross-sectional population survey conducted over a twelve month period on 4,636 non-institutionalized urban and rural New Zealand residents aged fifteen years and older. Survey data were collected in the participants' home and included: a self-administered qualitative food frequency questionnaire, including questions on food preparation habits; a three-pass 24-hour diet recall; interviewer-administered questions on diet supplement use, barriers to dietary change and participant perception of household food security; physical measurements including weight, height, three circumferences, two skinfolds and elbow breadth; blood pressure; and a blood sample to determine cholesterol and iron status.New methodologies developed for NNS97 included a computer based interview system, probability analyses for estimating prevalence of inadequate intake of selected nutrients, determination of iron status by both dietary and biochemical assessment, assessments of dietary supplement use and food security. A full range of quality control procedures at each stage of the data collection were also initiated.NNS97 has improved on previous New Zealand national nutrition survey methodologies, particularly with direct data capture and rigorous quality control procedures used in the collection of survey data.

To explore the concept of food security (when there is enough, appropriate and acceptable food available) in the adult New Zealand population using the National Nutrition Survey (NNS97).The stepwise development of indicators of food security included a literature search and focus groups with low income women and men. Key issues surrounding the procurement and provision of food were determined and eight indicator statements prepared for inclusion in NNS97, to be addressed by each participant on behalf of their household.Prevalence was significantly higher (p0.05) for females compared to males for the majority of indicator statements among New Zealand EuropeanOthers and Maori. New Zealand EuropeanOthers reported the most food security; Pacific people reported the least and Maori fell between the two. There was a significant increasing linear trend of food security with age (p0.001), after adjusting for gender. "Food runs out in my/our household due to lack of money" was cited more often by female compared to male New Zealand EuropeanOthers in NZDep96 quartiles III and IV.The issue of 'not having enough food' may be more prevalent in New Zealand than US or Australia. Among New Zealand EuropeanOthers the higher prevalence of insufficient food due to lack of money among females from NZDep96 quartiles III and IV suggests that males may be protected from this by their female partners. Food security needs to be improved among young adults, women, Maori and Pacific people in order to prevent longer term nutritional health consequences.

To measure the average serum concentration of total cholesterol and high density lipoprotein cholesterol in a representative sample of New Zealanders.Serum total and high density lipoprotein cholesterol levels were measured in a representative sample of 1,412 men and 1,741 :women aged 15 years or older who participated in the National Nutrition Survey (1997) of New Zealanders.The average serum total cholesterol concentration in men was the same as in women (5.7 mmol/L); however, younger women (44 years and under) tended to have lower levels and older women (55 years and over) higher levels of total cholesterol than men. Women in all age groups had higher average levels of high density lipoprotein cholesterol (1.4 mmol/L) than men (1.2 mmol/L). Ethnic differences were apparent with Maori men having significantly higher average levels of total cholesterol than their New Zealand European counterparts.Mean serum total cholesterol concentration in women has declined by 0.3 mmol/L from 6.0 mmol/L (p0.05) since the previous representative survey of New Zealanders (Life in New Zealand Survey, 1989), but by only 0.1 mmol/L in men, despite a similar reduction amongst men and women in the proportion of dietary energy derived from total and saturated fat. It is possible that weight gain in men and women during the last nine years is having a differential effect on serum cholesterol concentrations.

There have been few studies on urinary tract infections (UTIs) in adult males. This study aimed to look at the clinical features of males presenting with urinary tract infections in a predominantly gay general practice population.A retrospective audit and analysis was carried out of all male patients presenting with symptoms suggestive of a UTI and in whom a pathogen was cultured from urine. The subjects were drawn from two urban general practices in Melbourne. Subjects with known pre-existing urinary tract abnormalities, or in whom recent urinary tract instrumentation had been performed, were excluded, as were subjects in whom Neisseria gonorrhoeae was cultured from urine.Thirty-three subjects were identified, with a total of 47 presentations. Six subjects were excluded on the basis of pre-existing known factors which would predispose to UTIs, leaving 27 subjects, with 37 episodes of UTI. The mean age was 43 (range = 28-62) and 25 of the 27 identified as gay. Nine out of the 27 (33%) were HIV positive with a mean CD4 of 574/mm3 (range = 41-1812). The main presenting symptoms were dysuria/burning on micturition, urinary frequency, fever/sweats and haematuria. Urethral discharge occurred in two episodes. Multiple symptoms on presentation were common. The main organism cultured was E. coli. Fourteen subjects underwent further radiological investigation and two abnormalities were detected.Uncomplicated UTIs are uncommon in males presenting to general practice. The symptoms are similar to those in females with UTIs, though fever may be more common. Treatment with oral antibiotics in a primary care setting is generally curative. Further investigation of males with UTIs may be appropriate, but more studies are needed as to the cost-benefit of this.

Understanding the metabolic consequences of heart failure is important in evaluating potential mechanisms for disease progression and assessing targets for therapies designed to improve myocardial metabolism in patients with heart failure. PET is uniquely suited to noninvasively evaluate myocardial metabolism. In this study, we investigated the kinetics of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) and [18F]FDG in patients with stable New York Heart Association functional class III congestive heart failure and a left ventricular ejection fraction of no more than 35%.Twelve fasting patients underwent dynamic PET studies using [18F]FTHA and FDG. From the dynamic image data, the fractional uptake rates (Ki) were determined for [18F]FTHA and FDG. Subsequently, serum free fatty acid and glucose concentrations were used to calculate the myocardial free fatty acid and glucose uptake rates, respectively. Uptake rates were compared with reported values for [18F]FTHA and FDG in subjects with normal left ventricular function.The average Ki for [18F]FTHA was 19.7 +/- 9.3 mL/100 g/min (range, 7.2-36.0 ml/100 g/min). The average myocardial fatty acid use was 19.3 +/- 2.3 mmol/100 g/min. The average Ki for FDG was 1.5 +/- 0.37 mL/100 g/min (range, 0.1-3.3 mL/100 g/min), and the average myocardial glucose use was 12.3 +/- 2.3 mmol/100 g/min.Myocardial free fatty acid and glucose use in heart failure can be quantitatively assessed using PET with [18F]FTHA and FDG. Myocardial fatty acid uptake rates in heart failure are higher than expected for the normal heart, whereas myocardial glucose uptake rates are lower. This shift in myocardial substrate use may be an indication of impaired energy efficiency in the failing heart, providing a target for therapies directed at improving myocardial energy efficiency.

This study examined the reliability, validity, and responsiveness to change of measurements obtained with a 66-item version of the Gross Motor Function Measure (GMFM-66) developed using Rasch analysis.The validity of measurements obtained with the GMFM-66 was assessed by examining the hierarchy of items and the GMFM-66 scores for different groups of children from a stratified random community-based sample of 537 children with cerebral palsy (CP). A subset of 228 children who had been reassessed at 12 months was used to test the hypothesis that children who are young (5 years of age) and have "mild" CP will demonstrate greater change in GMFM-66 scores than children who are older ((5 years of age) and whose CP is more severe. Data from an additional 19 children with CP who were assessed twice, one week apart, were used to examine test-retest reliability.The overall changes in GMFM-66 scores over 12 months and a time ( severity ( age interaction supported our hypotheses. Test-retest reliability was high (intraclass correlation coefficient=.99).This study demonstrated that the GMFM-66 has good psychometric properties. By providing a hierarchical structure and interval scaling, the GMFM-66 can provide a better understanding of motor development for children with CP than the 88 item GMFM and can improve the scoring and interpretation of data obtained with the GMFM.

Patients with adult GH-deficiency are thought to have an increased risk of cardiovascular disease. Sialic acid (SA) concentrations have been proposed as a marker of atherosclerotic disease probably related to an inflammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH-deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated.We performed a randomised, double-blind placebo-controlled study in 18 patients with adult GH-deficiency before and after 3 months GH replacement therapy (0.036 U/kg/d; GH-treated group: 6 females, 3 males; age: 47.3 +/- 5.4 years., mean +/- SEM; placebo-group: 5 females, 4 males; mean age 50.2 +/- 4.7). In addition, SA concentrations were measured in 18 sex and age matched healthy control subjects.Blood samples were obtained after an overnight fast. Serum SA, triglycerides and cholesterol were measured using enzymatic methods. Lipoprotein classes were separated by ultracentrifugation. Insulin and IGF-I were determined by radioimmunoassay, HbA1C was measured by anion exchange liquid chromatography.SA concentrations of the patients with adult GH-deficiency were not significantly different compared to the control group (GH-deficient group: 2.29 +/- 0.02 mmol/l, mean +/- SEM vs. control group: 2.09 +/- 0.13 mmol/l, P = 0.25). Before GH replacement therapy SA concentrations correlated positively with the patients age (r = 0.45; P0.04) and fasting insulin concentrations (r = 0.5; P0.03) but not with fasting lipid profile. GH replacement therapy significantly increased IGF-I (GH: + 27 +/- 2.6 vs. placebo: + 1.0 +/- 0.8 nmol/l, P0.001) and fasting insulin concentrations (GH: + 71.9 +/- 8.0 vs. placebo: + 19.6 +/- 22.6 pmol/l, P0.04) compared to placebo therapy. SA concentrations (GH: - 0.41 +/- 0.15 vs. placebo: - 0.01 +/- 0.12 mmol/l, P0.05), total cholesterol (GH: - 0.71 +/- 0.16 vs. placebo: 0.23 +/- 0.21 mmol/l, P0.003) and LDL-cholesterol (- 0.71 +/- 0.14 vs. placebo: - 0.12 +/- 0.21 mmol/l P0.04) significantly decreased after GH replacement therapy compared to placebo therapy. No significant correlation between changes in SA concentrations and changes in lipid profile were observed following GH replacement therapy.These results suggest that, firstly, GH replacement therapy may have a beneficial effect on the pathogenesis of atherosclerosis despite the increase in insulin concentrations, a surrogate marker of insulin resistance, secondly, the proposed beneficial effect of GH on the atherosclerotic process is likely to be multifactorial and cannot only be explained by changes in lipid profile and finally, SA might be a useful marker for the process of atherosclerotic disease in interventional studies.

From the description above, the diversity of antibodies as a class of potential therapeutic agents is weighed against the constraints of developing any therapeutic molecule. Although much of this limit is specific to the antibody design, plant-based production systems have a potential to impact commercialization by making larger volume products manageable, with lower up-front capital requirements. Due to their novel glycosylation pattern (Faye et al. 1989), plants at present may not create antibodies with all the functions of mammalian-glycosylated antibodies (Wright and Morrison 1994). This is not a limit for all current products. Success is dependent on fusing the efficient agriculture infrastructure with the narrow tolerances required for a drug production system. Further validation of plants as a production system will come as more therapeutics from plants follow the corn-produced material through human clinical trials.

In binocular rivalry, the observer views two incongruent images, one through each eye, but is conscious of only one image at a time. The image that is perceptually dominant alternates every few seconds. We used this phenomenon to investigate neural correlates of conscious perception. We presented a red vertical grating to one eye and a blue horizontal grating to the other eye, with each grating continuously flickering at a distinct frequency (the frequency tag for that stimulus). Steady-state magnetic fields were recorded with a 148 sensor whole-head magnetometer while the subjects reported which grating was perceived. The power of the steady-state magnetic field at the frequency associated with a grating typically increased at multiple sensors when the grating was perceived. Changes in power related to perceptual dominance, presumably reflecting local neural synchronization, reached statistical significance at several sensors, including some positioned over occipital, temporal, and frontal cortices. To identify changes in synchronization between distinct brain areas that were related to perceptual dominance, we analyzed coherence between pairs of widely separated sensors. The results showed that when the stimulus was perceived there was a marked increase in both interhemispheric and intrahemispheric coherence at the stimulus frequency. This study demonstrates a direct correlation between the conscious perception of a visual stimulus and the synchronous activity of large populations of neocortical neurons as reflected by stimulus-evoked steady-state neuromagnetic fields.

Behavior problems of 44 children with Down syndrome between the ages of 6 and 15 and 44 controls without mental retardation matched for age, sex, and socioeconomic status were compared on the basis of mother and teacher ratings. Ratings from both sources indicated that children with Down syndrome had more behavior problems, in particular attention deficit, noncompliance, thought disorder, and social withdrawal. Life events from the past year were significantly associated with mother but not teacher ratings of Down syndrome behavior problems.

Insulin-like growth factor-I (IGF-I) has both insulin-like and anabolic actions but unlike insulin, IGF-I circulates bound to a number of specific binding proteins that regulate its availability and activity. Patients with type 1 diabetes mellitus have low levels of circulating IGF-I despite increased growth hormone (GH) secretion, and are a group that may benefit from rhIGF-I therapy. Understanding the relationship between IGF-I and its binding proteins is necessary to appreciate the actions of exogenously administered rhIGF-I. Therefore, we examined the effects of 19 days' subcutaneous administration of rhIGF-I (50 micrograms/kg BID) on the levels of IGF-I, IGF-II and the IGF-binding proteins (IGFBPs), as well as the daily dose of insulin necessary to maintain glycaemic control in patients with type 1 diabetes mellitus.This was an open study, and the patients were studied initially while resident (days 1-5) in the hospital and thereafter (days 6-24) as outpatients. Serum was collected at baseline and at intervals throughout the study for the measurement of total IGF-I, IGF-II, IGFBP-1, -2, -3, free insulin and growth hormone (GH). Daily insulin doses and glucometer readings were recorded throughout the study. The changes in each of these variables were examined. The subjects were six adults (35.3 +/- 4.0 years, mean +/- SE), with type 1 diabetes, and all had reasonable glycaemic control (HbA1c 7.2 +/- 0.5%).rhIGF-I administration increased circulating total IGF-I over two-fold (15.3 +/- 1.9 vs. 33.7 +/- 5.4 nmol/l, mean +/- SEM, P0.01, day 1 vs. day 20) and decreased plasma IGF-II concentration (85.0 +/- 4.7 vs. 50.6 +/- 4.7 nmol/l, P0.01, day 1 vs. day 20). The dose of insulin required for adequate glycaemic control decreased significantly during rhIGF-I therapy (46 +/- 7 vs. 31 +/- 8 U/day, P0.05, day -1 vs. day 19), as did the fasting free insulin concentration (8.4 +/- 1.5 vs. 5.0 +/- 0.8 mU/l, P0.05, baseline vs. day 5). IGFBP-2 concentration increased (388 +/- 115 vs. 758 +/- 219 micrograms/l, P0.05, day 1 vs. day 20), but IGFBP-1 and IGFBP-3 were unchanged during rhIGF-I treatment. Mean nocturnal GH concentration decreased (12.7 +/- 3.3 vs. 3.8 +/- 0.9 mU/l, P = 0.05) after 4 days' rhIGF-I therapy.Twice daily rhIGF-I therapy in adults with type 1 diabetes resulted in an increase in circulating IGF-I with a reciprocal decrease in IGF-II, and a marked elevation of IGFBP-2 concentration. The levels of IGFBP-1 and -3 were not dramatically changed despite a reduction in the concentration of serum free insulin, and a large decrease in the requirement for insulin. The mechanisms behind these changes remains unclear but alterations in circulating levels of of IGFBPs may alter IGF-I bioactivity. If rhIGF-I is to have an application in the management of adults with type 1 diabetes, further work is necessary to determine the metabolic consequences of the alterations seen in the IGFs and their binding proteins following rhIGF-I administration.

In genetic males, mutation of the 17beta-hydroxysteroid dehydrogenase 3 (17HSD3)gene that is normally expressed in the testes impairs testosterone formation and causes development of male pseudohermaphroditism. We have ascertained seven women who are sisters of men with 17HSD3 deficiency and who are either homozygotes or compound heterozygotes for the same mutations as their affected brothers. Our findings confirm the concept that women with such mutations are asymptomatic.

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P0.01). The total cholesterol concentration (P0.02), the low density lipoprotein cholesterol concentration (P0.02), and the VLDL cholesterol/VLDL apoB ratio (P0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.

A 49-year-old woman had a palpable mass in her occipital region. Plain radiographs and CT examination revealed extensive atlantooccipital pneumatization with findings consistent with the diagnosis of mastoid pneumocele. Decompression was achieved with placement of a myringotomy tube, resulting in prompt symptomatic relief. On a follow-up CT examination, the pneumatized areas had become opacified and new bone formation was present.

Three studies are described that assess elements of a new model of adolescent health-risk behavior, the prototype/willingness (P/W) model (F. X. GibbonsM. Gerrard, 1995, 1997). The 1st analysis examined whether a central element of the prototype model, behavioral willingness, adds significantly to behavioral expectation in predicting adolescents' smoking behavior. The 2nd set of analyses used structural-equation-modeling procedures to provide the 1st test of the complete model in predicting college students' pregnancy-risk behavior. Finally, the 3rd study used confirmatory factor analysis to assess the independence of elements of the model from similar elements in other health behavior models. Results of the 3 studies provided support for the prototype model and, in particular, for 2 of its primary contentions: (a) that much adolescent health-risk behavior is not planned and (b) that willingness and intention are related but independent constructs, each of which can be an antecedent to risk behavior.